“…A good rule of thumb is that molecules from an organism are nonimmunogenic to the same organism, are weakly immunogenic to organisms of the same species or phylogenetically close organisms, but strongly immunogenic to phylogenetically distant organisms. For example, a contributing factor to the potent immunogenicity of the keyhole limpet hemocyanin (KLH), a nonheme protein used as a carrier protein in antibody production, − is its “foreignness”. Hemocyanin is found in arthropods and mollusks, with KLH being derived from the hemolymph of the giant keyhole limpet, a mollusk that is phylogenetically distant from humans. , Also, bovine serum albumin is nonimmunogenic in cows but elicits a strong immune response in mice and rabbits. ,− However, it is important to note that immune responsiveness being predicated on self-vs foreign contrast is overly simplistic because some evolutionarily conserved biomolecules, such as collagen, are weakly immunogenic in organisms where they are “foreign”. − On the other hand, spermatozoa are strongly immunogenic in the same organisms where they are “self”. − Nevertheless, designing biomaterials with biomolecules from phylogenetically distant organisms to the target organism is another principle to impart immunomodulatory properties.…”